The objective of proposed research is to investigate the mechanism of the interaction of polymerizing fibrin with platelets and with other cells (fibroblasts, red cells and leukocytes), and the biological significance of this interaction. Platelets and undifferentiated fibroblasts adhere to polymerizing fibrin and promote fibrin polymerization but they do not adhere to fully polymerized fibrin. The significance of platelets and fibrin in hemostatic plugs in thrombi has long been appreciated but it has been assumed that their roles were additive rather than interactive. Specifically, the objectives of our project are: 1. Identification of component of platelet membranes which does interact with polymerizing fibrin; identification of specific inhibitors of fibrin-platelet reaction; study of the relationship between platelet-fibrin interaction and fibrin clot retraction. 2. Physicochemical characterization of polymerizing fibrin which interacts with platelets. 3. Comparison of platelet with other cells (fibroblasts, red cells, polymorphonuclear granulocytes) with respect to the interaction of fibrin. 4. Study of cell-fibrin interaction in pathological states involving platelets and other cells. 5. Effects of polymerizing fibrin on platelets and on other cells in vivo. For the purpose of the study, cells will be isolated from human or animal blood or prepared by tissue culture techniques. Key words: fibrin, platelet membranes, fibroblasts, hemostatic plug, fibrin-cell interaction. BIBLIOGRAPHIC REFERENCES: Niewiarowski, S. and Goldstein, S.: Fibrin clot retraction by human skin fibroblasts: Effects of ADP and thrombin, Proc. Soc. Exp. Biol. Med. 151: 253-256, 1976. Niewiarowski, S., Lowery, C.T., Hawiger, J., Millman M. and Timmons, S.: Immunoassay of human platelet factor 4 (PF4, antiheparin factor) by radialimmunodiffusion. J. Lab. Clin. Med. 87: 720-733, 1976.